Dynamique des sédiments fins en milieu marin et agitation portuaire

Mes travaux de recherche sous la direction du Professeur A. Grovel, ont fait l'objet d'une thèse de doctorat sous le titre : "Modélisation dans un estuaire à marée. Rôle du bouchon vaseux dans la tenue des sols sous marins", soutenue à l'université de Nantes le 10 juillet 1992, devant le jury composé par : M. Bélorgey, C. Larsonneur, J. Chapon, A. Graillot, A. Grovel et P. Jouve. Depuis 1992, les recherches que je mène se situent dans le cadre de l'hydraulique maritime appliquée aux travaux maritimes. Ces recherches concernent principalement les problèmes d'aménagement portuaire et côtier, car les résultats de celles-ci apportent des éléments de réflexion aux ingénieurs en génie côtier, lesquels doivent tenir compte des contraintes environnementales propres à chaque site dans la conception des ouvrages maritimes. Il se pose alors quatre types de problèmes indissociables :a) l'étude des conditions environnementales locales comprenant la mesure de la houle in situ, l'étude de la marée extrême locale et l'étude des couches sédimentaires mobilisables sous contraintes hydrodynamiques,b) l'étude de l'implantation des ouvrages de protection contre la houle afin d'assurer une navigation en toute sécurité garantie par une modélisation fine de l'agitation portuaire, tenant compte de la houle incidente et des réflexions de la houle par les frontières latérales,c) l'analyse de la stabilité d'ouvrages de génie civil nécessitant une connaissance approfondie de la houle de projet, de la marée, et de la tenue des sols marins,d) l'examen de l'impact sédimentaire causé par les ouvrages de protection sur les problèmes d'ensablement, d'envasement et d'érosion. Les trois principaux thèmes sur lesquels je travaille actuellement à la Faculté des Sciences et des Techniques de Nantes, sont tous liés aux problèmes décrits ci-dessus ; les deux premiers ont des points communs avec ma thèse de doctorat et le troisième est un thème de recherche que j'étudie depuis 1994. Ces trois thèmes sont :1) les processus sédimentaires des vases,2) les problèmes hydrosédimentaires dans les estuaires et les zones côtières,3) l'agitation portuaire. Ces thèmes sont développés respectivement dans les chapitres 1, 2 et 3 de ce mémoire, ensuite, les différentes activités liées à la recherche auxquelles j'ai participées depuis 1992 sont décrites au chapitre 4 et finalement les conclusions et perspectives sont présentées

Serine-Rich Repeat Protein adhesins from Lactobacillus reuteri display strain specific glycosylation profiles

Lactobacillus reuteri is a gut symbiont inhabiting the gastrointestinal tract of numerous vertebrates. The surface-exposed Serine-Rich Repeat Protein (SRRP) is a major adhesin in Gram-positive bacteria. Using lectin and sugar nucleotide profiling of wild-type or L. reuteri isogenic mutants, MALDI-ToF-MS, LC-MS and GC-MS analyses of SRRPs, we showed that L. reuteri strains 100-23C (from rodent) and ATCC 53608 (from pig) can perform protein O-glycosylation and modify SRRP100-23 and SRRP53608 with Hex-Glc-GlcNAc and di-GlcNAc moieties, respectively. Furthermore, in vivo glycoengineering in E. coli led to glycosylation of SRRP53608 variants with α-GlcNAc and GlcNAcβ(1→6)GlcNAcα moieties. The glycosyltransferases involved in the modification of these adhesins were identified within the SecA2/Y2 accessory secretion system and their sugar nucleotide preference determined by saturation transfer difference NMR spectroscopy and differential scanning fluorimetry. Together, these findings provide novel insights into the cellular O-protein glycosylation pathways of gut commensal bacteria and potential routes for glycoengineering applications

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types